SEPSISRyan Donlin, BSN, RN, CCRN

Flight Nurse – REACH 3/Napa, CA

Objectives• Review the basics of sepsis pathophysiology

• Review and discuss the evolution of sepsis as defined by the healthcare community

• Examine the early screening, identification and treatment pathways for sepsis

Objectives (cont.)

• Explore ways to fine tune treatment for sepsis patients requiring ICU level care

• Analyze the treatment differences for the pediatric population

• Recognize the psychosocial impacts of sepsis on both the patient and family

SEPSIS• A syndrome of physiologic, pathologic, and

biochemical abnormalities induced by infection• A normal inflammatory response that has gone

overboard• Major public health concern, accounting for more

than $20 billion (5.2%) of total US hospital costs in 2011

Contributing Factors• Larger aging population with more co-morbidities• Increased recognition • Rise in invasive procedures, immunosuppressive drug

use, chemotherapy, and organ transplants • Increasing antibiotic resistance

Impact of Sepsis• Patients who survive sepsis often have long-term

physical, psychological, and cognitive disabilities with significant health care and social implications

• Sepsis is a leading cause of mortality and critical illness worldwide

Sepsis Definition Timeline

1991: Sepsis-1• Sepsis results from a host’s systemic inflammatory

response syndrome (SIRS) to infection – Two or more of (SIRS Criteria)

• Temperature >38C or <36C• Heart rate >90/min• Respiratory rate >20/min or PaCO2 <32mmHg• White blood cell count >12 000/mm3 or <4000/mm3 or >10%

immature bands

1991: Sepsis-1

• Severe Sepsis - complicated by organ dysfunction

• Septic Shock - induced hypotension persisting despite adequate fluid resuscitation

2001: Sepsis-2• Task force gathered due to recognized limitations of

sepsis criteria– Result = expanded the list of diagnostic criteria

• Sepsis =General +

Hemodynamic +Inflammatory +

Organ Dysfunction +Tissue Perfusion Parameters

• Septic Shock - a state of acute circulatory failure

2012 – Sepsis 2.1

Expanded SIRS Criteria+

Suspicion of infection (does not need to be confirmed/proven)

=SEPSIS Criteria

2016: Sepsis-3

• Sepsis (new definition)– a life-threatening organ dysfunction caused by a

dysregulated host response to infection– SIRS and Severe Sepsis are no more for adults

2016: Sepsis-3 & SOFA• Organ Dysfunction - identified as an acute change in

total SOFA – Sequential [Sepsis-Related] Organ Failure Assessment

Sepsis 3

Sepsis 3• Septic Shock (new definition)- subset of sepsis in

which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality

• Clinical Indicators– Persisting hypotension requiring vasopressors to maintain

MAP > 65mmHg &– Serum lactate level >2 mmol/L (18mg/dL) despite adequate

volume resuscitation

SSC Response to Sepsis-3

• As of March 1, 2016• Utilize 2012 Surviving Sepsis Campaign

recommendations + new qSOFA/SOFA scoring system– tool for identifying patients at risk of sepsis with a higher

risk of hospital death or prolonged ICU stay both inside and outside critical care units.

BASIC BreakdownSepsis = suspected infection + SOFA + qSOFA

SO WHERE DO WE GO FROM HERE???

Recommendation is early screening,

early identification, and

early treatment

Step 1: Screen to Identify Infection

• Suspicion of infection (qSOFA)– Having 2 of 3 factors

What if I’m Prehospital EMS?• Utilize qSOFA assessment criteria + pt history

(especially recent illness/fever) to help identify need for early intervention

• The prehospital phase of care is a vital opportunity for early fluid admin/resuscitation mgmt– 20-30ml/kg crystalloid fluid bolus– Don’t delay IV start…if nothing looks good- Place IO and

get fluid boluses going.

What if I’m Prehospital EMS?• Placement of IV and IVF admin was associated with

a significant reduction in the odds of hospital mortality compared to no fluid or IV access among severe sepsis patients

• Early mgmt of hypotension (MAP < 65) is key to tissue perfusion– If protocols allow, start vasoactive medications early if

resuscitation is ineffective

Step 1: Screen to Identify Infection

• Obtain at least 2 sets of blood cultures (both aerobic and anaerobic bottles) before antimicrobial therapy

Administering broad-spectrum antibiotics as appropriate within 1hr of suspected sepsis

Example of Empiric Regimens

Table adapted from: UCSF Infectious Disease Management Program: http://clinicalpharmacy.ucsf.edu/idmp/guide_home.htm

ABX: Order of Administration

Gram-negative coverage • Piperacillin/tazoba

ctam• Meropenem• Aztreonam

Gram-positive coverage • Vancomycin• Linezolid

Double gram-negative coverage and/or antifungal coverage and/or misc.• Tobramycin (gram-neg)• Metronidazole (anaerobic)• Caspofungin (antifungal)

May infuse over 30 minutes

Vancomycin is infused ≥ 1 hour

Step 2: Screen for Organ Dysfunction

Baseline Sequential [Sepsis-related] Organ Failure Assessment

(SOFA)

Step 2: SOFA

Step 3: Identification and Mgmt of Initial Hypotension

• MAP < 65mmHg and/or serum Lactate > 4mmol/L• Treatment

– 20-30ml/kg Crystalloid fluid resuscitation

• Evaluate - reassessment of volume responsiveness or tissue perfusion

Quick Review: 3hr Sepsis Bundle GoalStep 1: Early Screen to identify infection

– qSOFA + Labs (Rainbow Panel) + Blood Cultures, then…– ABX w/in 1hr of suspected infection; broad spectrum until

cultures returnStep 2: Early Screen for organ dysfunction or for patients at risk (SOFA)Step 3: Early mgmt of initial hypotension

– MAP > 65mmHg or Lactate > 4mmol/L • 20-30ml/kg crystalloid fluid

Lactate…to be used as a tool• Lactate production in septic shock is not due to anaerobic metabolism or low oxygen delivery.

–It is largely driven by endogenous epinephrine stimulating aerobic glycolysis via beta-2 adrenergic receptors.

• An elevated lactate should not be blindly used as a trigger to increase oxygen delivery

Lactate (cont.)• Elevated lactate is useful to identify occult shock

– patients who are being maintained by a robust endogenous catecholamine release

• These patients are at increased risk for deterioration and require more aggressive care.

Goal to Prevent

Press the Gas!!!

MAP > 65mmHg

VasopressorTime!

Perfusion is key!

Other Vasoactive Agents• Epinephrine mcg/kg/min

• Vasopressin 0.04 units/minute – can be added to Norepinephrine (NE) with intent of either

raising MAP or decreasing NE dosage

• Dopamine– alternative vasopressor agent to NE only in highly selected

patients • eg, patients with low risk of tachyarrhythmias and absolute or

relative bradycardia

Inotropic Therapy?• A trial of Dobutamine infusion up to 20mcg/kg/min

can be administered or added to vasopressor (if in use) in the presence of – (a) myocardial dysfunction as suggested by elevated

cardiac filling pressures and low cardiac output, or – (b) ongoing signs of hypoperfusion, despite achieving

adequate intravascular volume and adequate MAP

• Warning – Addition of Dobutamine will reduce afterload.

Overall goals within first 6hrs (6hr Bundle Therapy)

Patient Required Intubation and Ventilator support…

• What extra goals are there now?– If ARDS criteria meet (P/F ratio – mild < 300, moderate <

200, severe < 100)– Target tidal volume 6ml/kg per IBW– Plateau Pressure < 30cmH20

PEEP This• Always have PEEP support – may need high PEEP

strategies with moderate/severe ARDS

• Goal is to prevent alveolar collapse and promote lung recruitment

• REACH ETT clamping protocol*

Still Intubated?

• HOB > 30-45 degrees + Oral chlorhexidinegluconate to reduce the risk of ventilator-associated pneumonia (VAP) in ICU pts w/ sepsis

• Prone Positioning?

• Conservative fluid resuscitation strategy!

ICU Time!

Let’s fine-tune the care: Misc. therapy goals

Endocrine –• Glycemic control < 180 mg/dL

– Consider insulin management therapy if Glucose >180mg/dL x2 consecutive checks

• Corticosteroids –– not recommended for the treatment of sepsis in Adults if

fluid resuscitation is adequate

Flush the pipes

Renal• CRRT = intermediate HD in patients w/ sepsis & ARF

– CRRT would be more beneficial in patients with hemodynamic instability

• Sodium Bicarbonate – not recommended to improve hemodynamics as it may

actually induce lactic acidemia

Feed Me!

Nutrition• Feed the gut!

– PO/Enteral, as tolerated, rather than either complete fasting or provision of only IV glucose within the first 48 hours after diagnosis

• Low dose feeding (e.g. up to 500 cals/day) during the first week

– Advance as tolerated

Body & Mind

Psych-Social• Discuss and set goals of care with patients and family as early as possible

– Especially if ICU admission is required, within first 72hrs

• Incorporate Palliative Care principles where appropriate and include goals of care in treatment plan

Be the DetectiveLocate/control the source of infection

• If intravascular access devices are a possible source, remove them promptly after other vascular access has been established• Utilize least invasive effective means as interventions for source control first.

– IR vs. Surgical approaches

Pediatric Population“They’re not just tiny adults”

• There is no equivalent to qSOFA/ SOFA yet adopted in the U.S. so we may still see SIRS used for Pedi

• Two or more of (SIRS Criteria)• Temperature >38C or <36C• Heart rate > 2SD above normal for age• Respiratory rate > 2SD above normal for age• Abnormal WBC count or >10% immature bands

Pediatric Considerations

• Treatment is similar to that of adults but with some subtle differences– Perfusion- Warm vs. Cold (peripheral vasodilatation vs.

vasoconstriction)• Warm - wide pulse pressure, bounding pulses, warm extremities• Cold - narrow pulse pressure, weak pulses, cold extremities due to

shunting to vital organs

Pediatric Considerations (cont.)

• Fluid Resuscitation- rapid delivery and reassessment– 20ml/kg crystalloid via “push-pull” manual method– May require up to 60ml/kg total fluid within first hour

Pediatric Considerations (cont.)• Don’t hold out on vasoactive therapy, but make the right

choice– Patient remains hypotensive after reaching 60ml/kg fluid resusitation

• Cold shock (SvO2 < 70%) – Epinephrine

• Warm shock (SvO2 > 70%) – NorEpi; consider adding Vasopressin

• Normotensive Cold shock (SvO2 < 70%)– impaired perfusion but normal BP– low dose Epinephrine + consideration of Milrinone/Dobutamine

Pediatric Considerations (cont.)• Hypoglycemia

– Neonates < 45mg/dL; Infants/Children < 60 mg/dL• Often an early indicator of adrenal insufficiency

• Hyperglycemia?• Hypocalcemia

– Infants <12 months of age may rely more heavily on extracellular calcium to maintain adequate cardiac contractility than older patients

Pediatric Considerations (cont.)

• Filled the tank and pressed the gas but refractory shock remains– Consider Adrenal insufficiency-

• 25-30% septic Pedi will have adrenal insufficiency known as Waterhouse-Friderichsen syndrome

– Hydrocortisone 1mg/kg bolus (max 100mg)

• Blood transfusion considered for Hgb < 10 g/dL

Pediatric Considerations (cont.)• Airway- provide 100% O2 via high flow (15L)

• Utilize non-invasive support if needed – CPAP/Bi-Level Positive Airway Pressure– Bubble CPAP (<10kg)

Case Study #1 – “My Tummy Hurts”• 3yr old previously healthy kiddo with c/o vomiting

for 2 days w/ fever. Tmax – 38.8C over the last 24hrs• Seen yesterday by PCP and sent home with Tylenol

with working diagnosis of “stomach virus” per Mom• PMH – none• Allergies – NKDA• Medications – Tylenol PRN• Family history – lives with both parents, older brother

at home with runny nose and cough

Case Study #1 (cont.)Primary survey/general appearance

– Ill appearing, drowsy, cries with stimulated

– Patent airway but rapid/shallow breathing pattern

– Pale skin tone, mottled distal extremities

Initial VitalsHR 166 BP 89/49 (62)RR 34 SPO2 – 91%

Temp 35.3

Case Study #1 (cont.)• Secondary Survey/Exam (notables)

– Poor cooperation w/ neuro exam, not oriented to place• Repeatedly says he’s at home

– Nasal congestion w/ “crusties”, dry mucus membranes– Diffuse ABD tenderness, mild guarding noted when

palpated– Cool, mottled extremities, Cap Refill > 4sec

• Notable labs –– FSBG 70, CO2 12, Anion gap 31, Cr 1.30– WBC 4.5 (0% Neutrophils / 89% Lymphocytes)

Case Study #1 (cont.)• Working diagnosis for patient?

– How sick is this patient?

• Critical concerns with regards to initial assessment and diagnostics?– Common manifestation of sepsis in pediatric population?– Assessment of end organ function?– Cold vs Warm shock? Treatment pathway…

• Any other imaging or diagnostics would you want completed?

Case Study #2 – “What Lies Beneath”

• 71 YOF w/ c/o uncontrolled LLE leg pain r/t chronic Cellulitis and diabetic ulcers

• Pt describes increased swelling and “heat” around LLE over the last 3 days, in addition to discoloration “different than anything before”

• PMH – COPD, CHF, Afib, DM Type II, HTN, HLD, Obesity, Smoker, ESRD w/ Dialysis

• PSH – Knee replacement, Ulcer debridement to bilateral feet,

• NKDA

Case Study #2Vital Signs –

• HR – 101 (Afib)• BP – 107/71• RR – 31• SPO2 – 90% RA• Temp – 39.1C• Pain – 8/10

• Pt describes decreased intake over the last 72hrs.

Case Study #2 (cont.)• What are our first steps upon ED admission?

• What could the working diagnosis be for this patient?

• Treatment needed to prevent further infection?

Case Study #3 – “The Brad”• Brad is a 34YOM who sustained a stab wound to the left flank

approx. 9 days ago following a “minor” dispute at a bar.

• Based off of the ABD-CT scan and MD eval, no surgical intervention was required r/t the initial injury.

• Brad was released home with pain meds and oral ABX.

“The Brad” (cont.)• Brad returned to the ED by family vehicle w/ a poor

presentation stating that the stab wound “won’t stop oozing” and “I can’t keep anything down”.

• PMH – Smoker ; PSH – none ; NKDA

• Home Meds – “just vitamins”

• Vital Signs –– HR: 103 ; BP: 96/62 (73) ; RR: 24 ; SPO2: 93% RA ; TEMP: 35.8C– Pain: 8/10 ; LOC: AOx4

• Working Dx – Hypovolemic shock, Dehydration, Possible Bowel Injury

“The Brad” (cont.)• Brad was immediately prepped and sent to the OR for an Ex

Lap• Anesthesia Report

– Intubated w/ 8.0 cuffed ETT for procedure– Meds: Sevoflourane, Sodabic, Fentanyl, Etomidate, Nimbex, Robinul,

Phenylephrine, Zosyn, Vancomycin, Norepinephrine– IVF: 4,000ml LR– EBL: minimal– UO: 2,300ml

• Surgical Report– 2 small bowel perforations: Resection + Primary anastomosis, NGT to

LIWS

“The Brad” (cont.) – To the ICU!!• Post Op ICU recovery phase was unremarkable until

POD #3• Brad slowly began to require and increase in pain

mgmt meds, decreasing hourly urine output, liable BPs during rest, and a low grade fever

• F/u ABD CT-scan and return to the OR theater revealed anastomotic leak and peritoneal abscess

• S/p procedure #2, Brad was difficult to wean from the vent d/t the development of ARDS stemming from aggressive fluid mgmt & AKI.

“The Brad” – Finale

• Brad’s total LOS in the hospital = 31 days– Days requiring mechanical

vent support – 13 days– OR procedures – 3

• Days away from the gym – 90 days

Take Home Concepts

• Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs

• A normal inflammatory response that has gone overboard

Take Home Concepts

• Sepsis is the primary cause of death r/t infection, especially if not recognized and treated promptly.

• Early recognition requires urgent attention especially in high risk populations– Neonates & Geriatric (> 85yrs) due to less physiologic

reserve

Take Home Concepts• New Sepsis-3 clinical criteria/definitions especially

qSOFA and SOFA are to be used as tools for predictors of mortality in a critically ill patient.

• Continue to be a clinical investigator for a variety of illnesses that may be present and use all the information collected as a guide to diagnosis and treatment

ReferencesAntonelli M, DeBacker D, Dorman T, et al. Surviving Sepsis Campaign Responds to Sepsis-3. 2016 Mar 1. http://www.survivingsepsis.org/SiteCollectionDocuments/SSC-Statements-Sepsis-Definitions-3-2016.pdf

Cummings, B. Treatment of Sepsis and Septic Shock in Children. 2016 Jan 7. http://emedicine.medscape.com/article/2072410-overview

Farkas, J, Weingart, S. Early norepinephrine to stabilize MAP in septic shock. 2014 Oct 6. http://emcrit.org/pulmcrit/early-norepinephrine-to-stabilize-map-in-septic-shock/

Farkas, J. PulmCrit- Top ten problems with the new sepsis definition. 2016 Feb 29. http://emcrit.org/pulmcrit/problems-sepsis-3-definition/

Farkas, J. Understanding lactate in sepsis & Using it to our advantage. 2015 July 5. http://emcrit.org/pulmcrit/understanding-lactate-in-sepsis-using-it-to-our-advantage/

Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003 Mar 28; 29: 530-538. http://www.esicm.org/upload/file4.pdf

Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23; 315(8):801-810. http://jama.jamanetwork.com/article.aspx?articleid=2492881

Surviving Sepsis Campaign

Weingart, S. www.EMCrit.org

Weiss, S. Pomerantz, W. Septic shock: Rapid recognition and initial resuscitation in children. 2015 Dec 22. http://www.uptodate.com/contents/septic-shock-rapid-recognition-and-initial-resuscitation-in-children